Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy.

Journal: 
Cancer Discov
Publication Year: 
2013
Authors: 
Chao Ma , Ann F Cheung , Thinle Chodon , Richard C Koya , Zhongqi Wu , Charles Ng , Earl Avramis , Alistair J Cochran , Owen N Witte , David Baltimore , Bartosz Chmielowski , James S Economou , Begonya Comin-Anduix , Antoni Ribas , James R Heath
Public Summary: 
Scientific Abstract: 
Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy.

© 2013 California Institute for Regenerative Medicine